Drosophila Hsp67Bc hot-spot variants alter muscle structure and function

• Published in: Cellular and molecular life sciences : CMLS Vol. 75; no. 23; pp. 4341 - 4356
• Main Authors: Jabłońska, Jadwiga, Dubińska-Magiera, Magda, Jagla, Teresa, Jagla, Krzysztof, Daczewska, Małgorzata
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-12-2018; Springer Nature B.V
• Subjects: Abnormalities; Aging; Amino Acid Sequence; Animals; Animals, Genetically Modified; Autophagy; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cytoskeleton; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Electron transport; Gene Expression; Heat shock proteins; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Insects; Larva - genetics; Larva - metabolism; Life Sciences; Maintenance; Microscopy, Electron, Transmission; Mimicry; Mitochondria; Motor Activity - genetics; Muscles; Muscles - metabolism; Mutation, Missense; Neuromuscular Junction - metabolism; Neuromuscular junctions; Original; Original Article; Phagocytosis; Polypeptides; Presynapse; Respiratory function; Sarcoplasmic Reticulum - metabolism; Sarcoplasmic Reticulum - ultrastructure; Sequence Homology, Amino Acid; Structure-function relationships; Hsp67Bc; sHSP; Development; Muscle; NMJ; Protein aggregates; Mutants; Drosophila
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-018-2875-z

The
Drosophila Hsp67Bc
gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromuscular junctions (NMJs), which implies its involvement in the maintenance of NMJ structure. Here, we report the effects of muscle-target overexpression of
Drosophila Hsp67Bc
hot-spot variants Hsp67BcR126E and Hsp67BcR126N mimicking pathogenic variants of human HSPB8. Depending on the substitutions, we observed a different impact on muscle structure and performance. Expression of Hsp67BcR126E affects larval motility, which may be caused by impairment of mitochondrial respiratory function and/or by NMJ abnormalities manifested by a decrease in the number of synaptic boutons. In contrast, Hsp67BcR126N appears to be an aggregate-prone variant, as reflected in excessive accumulation of mutant proteins and the formation of large aggregates with a lesser impact on muscle structure and performance compared to the Hsp67BcR126E variant.